The sphingolipid metabolic pathway yields highly active lipid signaling molecules that regulate many physiologic processes during development and for homeostasis in the adult. Furthermore, the pathway is highly regulated and appears to function abnormally in certain disordered states such as in cancer and in metabolic diseases. We are utilizing genetically altered mice that are modified in their sphingolipid metabolism and signaling to uncover new functions of sphingolipids in normal biology and in disease.